This study was aimed to investigate the changes of the hypothalamic-pituitary-adrenal axis (HPAA) activity and the
cytokines system in the hypothalamus of the depressive rats which were exposed to chronic unpredictable mild stressors (CUMS) after
middle cerebral artery occlusion (MCAO). By means of qRT-PCR, ELISA and Western blot,
mRNA and/or
protein expressions of
corticotropin releasing factor (CRF),
tumor necrosis factors-α (TNF-α), suppressor of
cytokines signaling 3 (SOCS3), phosphorylation of signal transducers and activators of transcription 3 (pSTAT3) were measured in the hypothalamus of rats. The results showed that, compared with control group, CUMS+MCAO group exhibited increased
mRNA levels of CRF, TNF-α, SOCS3, as well as up-regulated CRF, TNF-α, SOCS3 and pSTAT3
protein expressions. Furthermore, there were correlations between CRF and TNF-α, TNF-α and SOCS3, SOCS3 and pSTAT3, respectively. These observations indicated the CRF system was activated in the post
stroke depression (PSD) status. The TNF-α and its signaling pathway, STAT3/SOCS3, were up-regulated in
mRNA and
protein levels. In conclusion, this study presents the evidence which supports the hypothesis of signaling cross-talk between the CRF system and TNF-α signaling pathway after
ischemic stroke and CUMS.